We propose to continue our investigations on sphingolipid metabolism in the nervous system. Sphingolipids are indispensable components of myelin, synaptosomes and other membranes in the brain. The unequivocal elucidation of metabolic pathways of these compounds is essential for our understanding of brain metabolism and function. During the past two years, we have for the first time demonstrated that 3-ketoceramide (N-lignoceroyl 3-ketosphingosine) is converted into ceramide and various other sphingolipids in both brain and liver. We will further confirm this conversion in the brain and study the enzyme which catalyzes such conversion. During the study of the above conversion, we obtained evidence which strongly suggests that fatty acid exchange may be actively occurring with various sphingolipids in brain, liver and possibly in other tissues. We propose to study this exchange reaction in detail both in vivo and in vitro levels. Full understanding of sphingolipid metabolism in the brain is hampered by the fact that most of the enzymes involved in the synthesis of sphingolipids are not purified and poorly understood. Our investigation on gamma-hydroxylation of long chain fatty acids indicated possible existence of an alternative pathway of cerebroside synthesis. We propose to study synthesis of ceramide, cerebroside, and sphingomyelin in brain by purifying enzymes involved with a new approach.